Seriously ill infants with a suspected genetic disorder should undergo genome sequencing (GS) as a first-line genetic test rather than the current standard of care that can take months or years to play out, researchers reported recently in Genetics in Medicine, the official journal of the American College of Medical Genetics and Genomics (ACMG).

The recommendation was the conclusion of a three-year study of patients in neonatal intensive care units (NICUs) in Southern U.S. hospitals, including Louisville. The researchers targeted NICUs with a strong representation of African American infants and those from rural communities that often lack access to genetic services.

“Our results show the utility of GS because it provides early-in-life detection of clinically relevant genetic variations not detected by current clinical genetic testing, particularly for infants exhibiting certain phenotypic features,” the authors wrote in “Genome Sequencing as a First-line Diagnostic Test for Hospitalized Infants.”

Early diagnosis can have short-term benefits with regard to disease management and can shorten the lengthy diagnostic times that often are associated with symptoms of rare diseases. Routine front-line GS testing also can uncover conditions in infants with congenital heart malformations who would not have been tested previously because they lacked outward appearances such as abnormal craniofacial, ophthalmologic, auditory, or skin and hair features, the authors wrote.

The study’s authors included:

• Kelly E. Jackson, M.S., CGC, manager of genetic services at Norton Children’s Genetics Center, affiliated with the UofL School of Medicine, and an assistant professor of pediatrics at the University of Louisville School of Medicine
• Sarah L. Deans, R.N., clinical research nurse at the UofL School of Medicine
• Kyle B. Brothers, M.D., Ph.D., chief scientific officer for the Norton Children’s Research Institute, affiliated with the UofL School of Medicine, and endowed chair in Pediatric Clinical and Translational Research in the Department of Pediatrics at the UofL School of Medicine

The report was part of an ongoing study known as SouthSeq that is examining the benefits of genome sequencing in Southern states. SouthSeq is a part of the Clinical Sequencing Evidence-Generating Research (CSER) Consortium which is funded by the National Human Genome Research Institute (NHGRI), one of the institutes that make up the National Institutes of Health (NIH).

Additional work at Norton Children’s is to understand the possible usefulness of genome sequencing for families and health care providers. It was recently announced that NHGRI is funding a four-year project led by Dr. Brothers. This project will study whether community professionals like physical therapists, speech therapists and special education teachers are able to provide better care to children as a result of getting a genetic diagnosis.

Investigators also involved in this work include Gregory N. Barnes, M.D., Ph.D., Norton Children’s Neuroscience Institute, affiliated with the UofL School of Medicine; Deborah Davis, Norton Children’s Research Institute; Alexander Asamoah, M.D., Ph.D., Norton Children’s Genetics Center; and Kelly E. Jackson, the center’s manager of genetics services.

Recent research from Dr. Brothers

Recent research from Kelly E. Jackson